bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating blood culture collection practice in children hospitalized with acute illness at a tertiary hospital in Malawi
Authors: Mukhula Victoria Temwanani , Harawa Philliness Prisca , Phiri Chisomo , Khoswe Stanley , Mbale Emmie , Tigoi Caroline , Walson Judd L , Berkley James A , Bandsma Robert , Iroh Tam Pui-Ying , Voskuijl Wieger
Published: December 2023

Background

Blood culture collection practice in low-resource settings where routine blood culture collection is available has not been previously described.

Methodology

We conducted a secondary descriptive analysis of children aged 2–23 months enrolled in the Malawi Childhood Acute Illness and Nutrition (CHAIN) study, stratified by whether an admission blood culture had been undertaken and by nutritional status. Chi-square test was used to compare the differences between groups.

Results

A total of 347 children were included, of whom 161 (46%) had a blood culture collected. Children who had a blood culture collected, compared to those who did not, were more likely to present with sepsis (43% vs. 20%, p < 0.001), gastroenteritis (43% vs. 26%, p < 0.001), fever (86% vs. 73%, p = 0.004), and with poor feeding/weight loss (30% vs. 18%, p = 0.008). In addition, hospital stay in those who had a blood culture was, on average, 2 days longer (p = 0.019). No difference in mortality was observed between those who did and did not have a blood culture obtained.

Conclusion

Blood culture collection was more frequent in children with sepsis and gastroenteritis, but was not associated with mortality. In low-resource settings, developing criteria for blood culture based on risk factors rather than clinician judgement may better utilize the existing resources.
2021 European Resuscitation Council/European Society of Intensive Care Medicine Algorithm for Prognostication of Poor Neurological Outcome After Cardiac Arrest—Can Entry Criteria Be Broadened?*
Authors: Arctaedius Isabelle , Levin Helena , Larsson Melker , Friberg Hans , Cronberg Tobias , Nielsen Niklas , Moseby-Knappe Marion , Lybeck Anna
Published: December 2023

OBJECTIVES:

To explore broadened entry criteria of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) algorithm for neuroprognostication including patients with ongoing sedation and Glasgow Coma Scale-Motor score (GCS-M) scores 4–5.

DESIGN:

Retrospective multicenter observational study.

SETTING:

Four ICUs, Skane, Sweden.

PATIENTS:

Postcardiac arrest patients managed at targeted temperature 36°C, 2014–2018. Neurologic outcome was assessed after 2–6 months according to the Cerebral Performance Category scale.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

In 794 included patients, median age was 69.5 years (interquartile range, 60.6–77.0 yr), 241 (30.4%) were female, 550 (69.3%) had an out-of-hospital cardiac arrest, and 314 (41.3%) had a shockable rhythm. Four hundred ninety-five patients were dead at follow-up, 330 of 495 died after a decision on withdrawal of life-sustaining therapies. At 72 hours after cardiac arrest 218 patients remained unconscious. The entry criteria of the original algorithm (GCS-M 1–3) was fulfilled by 163 patients and 115 patients with poor outcome were identified, with false positive rate (FPR) of 0% (95% CI, 0–79.4%) and sensitivity of 71.0% (95% CI, 63.6–77.4%). Inclusion of patients with ongoing sedation identified another 13 patients with poor outcome, generating FPR of 0% (95% CI, 0–65.8%) and sensitivity of 69.6% (95% CI, 62.6–75.8%). Inclusion of all unconscious patients (GCS-M 1–5), regardless of sedation, identified one additional patient, generating FPR of 0% (95% CI, 0–22.8) and sensitivity of 62.9% (95% CI, 56.1–69.2). The few patients with true negative prediction (patients with good outcome not fulfilling guideline criteria of a poor outcome) generated wide 95% CI for FPR.

CONCLUSION:

The 2021 ERC/ESICM algorithm for neuroprognostication predicted poor neurologic outcome with a FPR of 0%. Broadening inclusion criteria to include all unconscious patients regardless of ongoing sedation identified an additional small number of patients with poor outcome but did not affect the FPR. Results are limited by high rate of withdrawal of life-sustaining therapies and few patients with true negative prediction.
Smartphone sensor data estimate alcohol craving in a cohort of patients with alcohol-associated liver disease and alcohol use disorder
Authors: Wu Tiffany , Sherman Garrick , Giorgi Salvatore , Thanneeru Priya , Ungar Lyle H. , Kamath Patrick S. , Simonetto Douglas A. , Curtis Brenda L. , Shah Vijay H.
Published: December 2023

Background:

Sensors within smartphones, such as accelerometer and location, can describe longitudinal markers of behavior as represented through devices in a method called digital phenotyping. This study aimed to assess the feasibility of digital phenotyping for patients with alcohol-associated liver disease and alcohol use disorder, determine correlations between smartphone data and alcohol craving, and establish power assessment for future studies to prognosticate clinical outcomes.

Methods:

A total of 24 individuals with alcohol-associated liver disease and alcohol use disorder were instructed to download the AWARE application to collect continuous sensor data and complete daily ecological momentary assessments on alcohol craving and mood for up to 30 days. Data from sensor streams were processed into features like accelerometer magnitude, number of calls, and location entropy, which were used for statistical analysis. We used repeated measures correlation for longitudinal data to evaluate associations between sensors and ecological momentary assessments and standard Pearson correlation to evaluate within-individual relationships between sensors and craving.

Results:

Alcohol craving significantly correlated with mood obtained from ecological momentary assessments. Across all sensors, features associated with craving were also significantly correlated with all moods (eg, loneliness and stress) except boredom. Individual-level analysis revealed significant relationships between craving and features of location entropy and average accelerometer magnitude.

Conclusions:

Smartphone sensors may serve as markers for alcohol craving and mood in alcohol-associated liver disease and alcohol use disorder. Findings suggest that location-based and accelerometer-based features may be associated with alcohol craving. However, data missingness and low participant retention remain challenges. Future studies are needed for further digital phenotyping of relapse risk and progression of liver disease.
Lack of detection of SARS-CoV-2 in British wildlife 2020–21 and first description of a stoat (Mustela erminea) Minacovirus
Authors: Apaa Ternenge , Withers Amy J. , Mackenzie Laura , Staley Ceri , Dessi Nicola , Blanchard Adam , Bennett Malcolm , Bremner-Harrison Samantha , Chadwick Elizabeth A. , Hailer Frank , Harrison Stephen W. R. , Lambin Xavier , Loose Matthew , Mathews Fiona , Tarlinton Rachael
Published: December 2023

Repeat spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into new hosts has highlighted the critical role of cross-species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spillover include Mustelidae (mink, ferrets and related animals), cricetid rodents (hamsters and related animals), felids (domestic cats and related animals) and white-tailed deer. These predispositions led us to screen British wildlife with sarbecovirus-specific quantitative PCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spillover was occurring. Fourteen wildlife species (n=402) were tested, including: two red foxes (Vulpes vulpes), 101 badgers (Meles meles), two wild American mink (Neogale vison), 41 pine marten (Martes martes), two weasels (Mustela nivalis), seven stoats (Mustela erminea), 108 water voles (Arvicola amphibius), 39 bank voles (Myodes glareolous), 10 field voles (Microtus agrestis), 15 wood mice (Apodemus sylvaticus), one common shrew (Sorex aranaeus), two pygmy shrews (Sorex minutus), two hedgehogs (Erinaceus europaeus) and 75 Eurasian otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, but a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
Neural Trajectories of Conceptually Related Events
Authors: Schafer Matthew , Kamilar-Britt Philip , Sahani Vyoma , Bachi Keren , Schiller Daniela
Published: December 2023

In a series of conceptually related episodes, meaning arises from the link between these events rather than from each event individually. How does the brain keep track of conceptually related sequences of events (i.e., conceptual trajectories)? In a particular kind of conceptual trajectory—a social relationship—meaning arises from a specific sequence of interactions. To test whether such abstract sequences are neurally tracked, we had participants complete a naturalistic narrative-based social interaction game, during functional magnetic resonance imaging. We modeled the simulated relationships as trajectories through an abstract affiliation and power space. In two independent samples, we found evidence of individual social relationships being tracked with unique sequences of hippocampal states. The neural states corresponded to the accumulated trial-to-trial affiliation and power relations between the participant and each character, such that each relationship’s history was captured by its own neural trajectory. Each relationship had its own sequence of states, and all relationships were embedded within the same manifold. As such, we show that the hippocampus represents social relationships with ordered sequences of low-dimensional neural patterns. The number of distinct clusters of states on this manifold is also related to social function, as measured by the size of real-world social networks. These results suggest that our evolving relationships with others are represented in trajectory-like neural patterns.
Role ofDusp5 KO on Vascular Properties of Middle Cerebral Artery in Rats
Authors: Tang Chengyun , Zhang Huawei , Border Jane J. , Liu Yedan , Fang Xing , Jefferson Joshua R. , Gregory Andrew , Johnson Claire , Lee Tae Jin , Bai Shan , Sharma Ashok , Shin Seung Min , Yu Hongwei , Roman Richard J. , Fan Fan
Published: December 2023

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) ofDusp5enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed thatDusp5KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) inDusp5KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable betweenDusp5KO and control rats. The internal elastic lamina in the MCA ofDusp5KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA inDusp5KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that whileDusp5KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging.
Nanoscale photobiotinylation, pulldown and sequencing of region-specific DNA from intact cells
Authors: Roberts Thomas C. , Kushner Max , Crowley Jack C. , Ozer Abdullah , Wang Juan , Ray Judhajeet , Lis John T. , Zipfel Warren R.
Published: December 2023

Femto-seq is a novel nanoscale optical method that can be used to obtain DNA sequence information from targeted regions around a specific locus or other nuclear regions of interest. Two-photon excitation is used to photobiotinylate femtoliter volumes of chromatin within the nucleus, allowing for subsequent isolation and sequencing of DNA, and bioinformatic mapping of any nuclear region of interest in a select set of cells from a heterogenous population.
Epithelial N-methyl-D-aspartate (NMDA) receptors mediate renal vasodilation by affecting kidney autoregulation
Authors: Romero Cesar A. , Lim Jasmine , Wang Hong , Wynne Brandi M. , Ma Peipei , Jing Yao , Liotta Dennis C. , D’Erasmo Michael , Traynelis Stephen F. , Eaton Douglas C. , Wall Susan M.
Published: December 2023

Background

N-methyl-D-aspartate receptor (NMDAR) are amino acid receptors that are well studied in brain physiology; however, their role in kidney is poorly understood. Nonetheless, NMDAR inhibitors can increase serum K+ and reduce GFR, which suggests they have an important physiological role in the kidney. We hypothesized that NMDARs in the distal nephron induce afferent-arteriole vasodilation through the vasodilator mechanism connecting-tubule-glomerular feedback (CNTGF) that involves ENaC activation.

Methods and results

Using a tubule-specific transcriptome database combined with molecular biology and microscopy techniques, we showed kidney expression of NMDAR subunits along the nephron and specifically in ENaC-positive cells. This receptor is expressed in both male and female mice, with higher abundance in females (p=0.02). Microperfusing NMDAR agonists into the connecting tubule induced afferent-arteriole vasodilation (EC5010.7 vs. 24.5 mM; p<0.001) that was blunted or eliminated with the use of NMDAR blocker MK-801 or with the ENaC inhibitor Benzamil, indicating a dependence on CNTGF of the NMDAR-induced vasodilation. In vivo, we confirmed this CNTGF-associated vasodilation using kidney micropuncture (Stop-flow pressure 37.9±2.6 vs. 28.6±1.9 mmHg, NMDAR agonist vs vehicle; p<0.01). We explored NMDAR and ENaC channel interaction by using mpkCCD cells and split-open connecting tubules. We observed increased amiloride-sensitive current following NMDAR activation that was prevented by MK-801 (1.14 vs. 0.4μAmp; p=0.03). In split-open tubules, NMDAR activation increased ENaC activity (Npo Vehicle vs. NMDA; p=0.04).

Conclusion

NMDARs are expressed along the nephron, including ENaC-positive cells, with higher expression in females. Epithelial NMDAR mediates renal vasodilation through the connecting-tubule-glomerular feedback, by increasing ENaC activity.
Impact of ectopic calcification on vascular oxygenation in placental dysfunction models: Simultaneousin vivoassessment with multi-parametric ultrasound and photoacoustic imaging
Authors: Edwards Skye A. , Correia-Branco Ana , Sankepalle Deeksha M. , Arora Aayush , Sweeney Allison , Solomon Patrick R. , Wallingford Mary C. , Mallidi Srivalleesha
Published: December 2023

Preeclampsia (PE) is a prevalent gestational disorder occurring in 2-10% of all pregnancies. It is associated with placental dysfunction which can result in maternal mortality and preterm birth. Despite scientific advances, the underlying mechanisms of PE and the progression of placental dysfunction remain poorly understood without preventative or curative treatment. Other than blood tests and postdelivery placental diagnostics, there are limited detection methods for monitoring placental health. A major roadblock is the lack of imaging modalities available to monitor placental hemodynamics, as the commonly used clinical imaging systems are either harmful due to ionizing sources, too expensive and inaccessible, or provide insufficient data. We propose the combination of quantitative ultrasound and photoacoustic imaging (QUSPAI) to characterize the material and structural changes of the placenta during pregnancy in normal and disease states. The Slc20a2 murine model of placental dysfunction has previously been characterized by increased ectopic placental vascular calcification, reduced fetal growth, and decreased postnatal bone mineral density. In this study we utilized the Slc20a2 model and imaged knockout (KO) and wildtype (WT) placentae on embryonic day (E)18.5. The dual-wavelength images and radio frequency data were collectedin vivoandex vivoto provide quantitative ultrasound spectral (QUS) parameters and blood oxygen saturation. The photoacoustic images indicated that the WT tissue had statistically higher blood oxygen saturation (StO2) values than the KO tissues while QUS data revealed strain-specific calcification effects. Building upon the E18.5 gestation data collected here, future work will involve monitoring longitudinal changes in these parameters, including early calcification, to support translating this method for early diagnosis of placental vascular diseases.
Geometric experience sculpts the development and dynamics of hippocampal sequential cell assemblies
Authors: Farooq Usman , Dragoi George
Published: December 2023

Euclidean space is the fabric of the world we live in. Whether and how geometric experience shapes our spatial-temporal representations of the world remained unknown. We deprived rats of experience with crucial features of Euclidean geometry by rearing them inside translucent spheres, and compared activity of large hippocampal neuronal ensembles during navigation and sleep with that of cuboid cage-reared controls. Sphere-rearing from birth permitted emergence of accurate neuronal ensemble spatial codes and preconfigured and plastic time-compressed neuronal sequences. However, sphere-rearing led to diminished individual place cell tuning, similar neuronal mapping of different track ends/corners, and impaired neuronal pattern separation and plasticity of multiple linear track experiences, partly driven by reduced preconfigured network repertoires. Subsequent experience with multiple linear environments over four days largely reversed these effects, substantiating the role of geometric experience on hippocampal neural development. Thus, early-life experience with Euclidean geometry enriches the hippocampal repertoire of preconfigured neuronal patterns selected toward unique representation and discrimination of multiple linear environments.
The influence of sidedness in unilateral cleft lip and palate on mid facial growth at 5 years of age
Authors: Fell Matthew , Chong David , Parmar Paras , Su Ting-Li , Enocson Lars , Richard Bruce
Published: December 2023

Objective

To determine whether facial growth at five years is different for children with a right versus left sided cleft lip and palate.

Design

Retrospective cohort study

Setting

Nine UK cleft centres

Patients

Patients born between 2000-2014 with a complete unilateral cleft lip and palate (UCLP)

Main outcomes measure

5-Year-Old’s Index scores

Results

378 children were included. 122 (32%) had a right sided UCLP and 256 (68%) had a left sided UCLP. 5-Year-Old’s index scores ranged from 1 (good) to 5 (poor). There was a higher proportion of patients getting good scores (1 and 2) in left UCLP (43%) compared to right UCLP (37%) but there was weak evidence for a difference (Adjusted summary odds ratio 1.27, 95% CI 0.87 to 1.87; P=0.22).

Conclusions

Whilst maxillary growth may be different for left versus right sided UCLP, definitive analysis requires older growth indices and arch forms.
Characterization of oscillations in the brain and cerebrospinal fluid using ultra-high field magnetic resonance imaging
Authors: Martins Tiago , Santini Tales , de Almeida Bruno , Wu Minjie , Wilckens Kristine A. , Minhas Davneet , Ibinson James W. , Aizenstein Howard J. , Ibrahim Tamer S.
Published: December 2023

Development of innovative non-invasive neuroimaging methods and biomarkers are critical for studying brain disease. In this work, we have developed a methodology to characterize the frequency responses and spatial localization of oscillations and movements of cerebrospinal fluid (CSF) flow in the human brain. Using 7 Tesla human MRI and ultrafast echo-planar imaging (EPI),in-vivoimages were obtained to capture CSF oscillations and movements. Physiological data was simultaneously collected and correlated with the 7T MR data. The primary components of CSF oscillations were identified using spectral analysis (with frequency bands identified around 0.3Hz, 1.2Hz and 2.4Hz) and were mapped spatially and temporally onto the MR image domain and temporally onto the physiological domain. The developed methodology shows a good consistency and repeatability (standard deviation of 0.052 and 0.078 for 0.3Hz and 1.2Hz bands respectively)in-vivofor potential brain dynamics and CSF flow and clearance studies.
Lower risk of dementia with Lewy bodies among users of glycolysis enhancing drugs in a new user, active comparator design
Authors: Hart Alexander , Aldridge Georgina , Zhang Qiang , Narayanan Nandakumar S. , Simmering Jacob E.
Published: December 2023

Background

Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key ATP-producing enzyme in glycolysis. Recent work has suggested a potentially neuroprotective effect of use of Tz/Dz/Az in Parkinson’s disease in both animal and human studies. We investigated neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB).

Methods

We used a new user active comparator design in the merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or two comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitors (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed the matched cohorts forward to estimate the hazard of developing DLB.

Results

Men who were newly started on Tz/Dz/Az had lower hazard of developing DLB then matched men taking tamsulosin (HR=0.60, p<0.001) or 5ARI (HR=0.73, p=0.012) while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (HR=1.17, p=0.12). These results were robust to several sensitivity analyses.

Conclusions

These data demonstrate that Tz/Dz/Az in decreases the risk of DLB. When combined with the literature of Tz/Dz/Az on PD, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. These observational associations must be further evaluated for causality in future randomized trials.
Factors Influencing Integrated Disease Surveillance and Response System in selected Districts in the Eastern Region of Ghana
Authors: Twene Paul , Sarfo Bismark , Yawson Alfred A. E , Otoo John Ekow , Asraku Annette
Published: December 2023

Background

Ghana adopted the Integrated Disease Surveillance and Response (IDSR) system, which is an integration of the various programs in the surveillance system and can contain disease outbreaks and pandemics. Implementation of the IDSR is influenced by several factors which can affect its functionality and ability to contain disease outbreaks. This study assessed the factors influencing the IDSR system in selected districts in the Eastern Region of Ghana.

Method

A cross-sectional study was conducted between February-March, 2022 in Fanteakwa North, Abuakwa South and New Juaben South districts in the Eastern Region of Ghana among health care workers who are involved in IDRS activities. Both primary and secondary data were collected and analyzed using descriptive statistics and regression analysis at 0.05 significant level with 95% confidence interval.

Results

Three hundred and forty-seven (347) health care workers participated in the study with 56.2% (195/347) indicating that rumor registers were available at the health facilities. Most of the respondents (64.8%, 225/347) had means of transport for disease surveillance activities while majority (61.9%, 215/347) had case-based forms for case investigation. About half (51.9%, 180/347) of the participants revealed that they did not receive any feedback from the next higher level in the past year. Availability of transport for IDSR activities was almost 3.4 times more likely to contribute positively to IDSR system compared to facilities without transport (AOR= 3.36; 95% CI= 1.44-7.83; p=0.005). Respondents who have the capacity to apply case definition are 2 times more likely to contribute to an effective IDSR system compared to health workers who cannot apply case definition (AOR= 1.94; 95% CI= 1.17-3.21; p=0.013). Respondents who did not receive feedback from the next higher level were 52% less likely to have an effective IDSR system compared to respondents who received feedback from the next higher level (AOR= 0.48; 95% CI= 0.23-1.00; p= 0.05).

Conclusion

Effective operation of IDSR is affected by the application of case definition and means of transport at health facilities. In addition, the capacity of health care workers to provide feedback can influence the smooth operation of the IDSR in the studied area in Ghana.
Does Women Empowerment alone Influence Contraception utilization in Bangladesh perspective? Findings from demographic health survey 2017-18 using A SEM analysis
Authors: Sarwer Md. Nawal , Jahan Effat Ara , Chowdhury Akibul Islam
Published: December 2023

Background

Women empowerment is a crucial issue that is less studied as a factor of contraception use among married women which helps to achieve sustainable development goals (SDGs). The present study aims to assess the relationship between women empowerment and contraception use.

Methods

This cross-sectional study used Bangladesh Demographic and Health Survey data 2017-18 which included 12006 (weighted) women aged from 15-49 years old. Hierarchical logistic regression and structural equation model (SEM) were used to show the relationship between women empowerment and contraception use.

Results

Overall, the tend to using contraception was increased with increased age, urban residence, increased wealth index and education level of both husband and wife. The findings from regression model showed that women empowerment in terms of women decision making, attitude to violence and social independence significantly influence the contraception use after controlling the covariates (p<0.05). SEM analysis showed negative relationship with overall women empowerment and contraception use (β= -0.138) which was not significant (p>0.05).

Conclusion

This study implies that greater women empowerment may not always act as stronger determinant for using contraception, and therefore other contributing factors such as age, education, religion, husband’s participation, joined decision making, economic status and couple relationship should be warranted.
"We have our reasons": Exploring the acceptability of pre-exposure prophylaxis among gay, bisexual, and other men who have sex with men in Ghana
Authors: Aidoo-Frimpong Gloria , Abu-Ba’are Gamji Rabiu , Apreku Amos , Amoh-Otu Richard Panix , Zigah Edem , Amu-Adu Prince , Amuah Samuel , Nyblade Laura , Torpey Kwasi , Nelson LaRon E.
Published: December 2023

Ghanaian men who have sex with men (MSM) face significant HIV disparities. Pre-exposure prophylaxis (PrEP) is a highly effective tool for HIV prevention. Previous studies on the perspectives of PrEP use among Ghanaian MSM identified high interest in PrEP among this population. However, the knowledge from the previous research, which was the best available evidence at the time, was primarily hypothetical because those data were collected before any real-world implementation of PrEP in Ghana. The purpose of the analysis is to identify and understand the factors currently influencing PrEP acceptance. We conducted a secondary analysis of focus group (n=8) data with Ghanaian MSM. Audio transcripts were subjected to descriptive thematic analysis. There was an almost universal awareness of PrEP, but inaccuracies about PrEP were common. PrEP acceptability was influenced by a mix of individual and intrapersonal factors. To bridge the gap between awareness, knowledge, and acceptability, HIV prevention programs should address access barriers and incorporate community-derived strategies.
Analysis of potential iron toxicity in hemodialysis patients under intravenous iron treatment
Authors: Peña-Esparragoza Jessy Korina , Chávez Guillén Alina , Ramos López Paloma , Rueda Elías Oscar , López Ongil Susana , Alique Matilde , Ramírez-Chamond Rafael , Carracedo Julia , Rodríguez-Puyol Diego , Martínez Miguel Patricia
Published: December 2023

Background

The use of higher doses of iron for the treatment of anemia in hemodialysis patients allows lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity.

Methods

Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles according to hepatic iron deposition, plasma protein oxidative stress was quantified, as well as iron and cytokine levels in peripheral blood mononuclear cells (PBMCs).

Results

Patients with higher hepatic iron deposition had a longer time on hemodialysis (41.0±44.9 vs 4.9±3.4 months, p<0.001) and higher ferritin levels (1181±532 vs 429±278 ng/ml, p<0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition.

Conclusions

Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed; therefore, more proactive treatment with intravenous iron to improve anemia management may not necessarily induce deleterious effects in hemodialysis patients.
Initial data analysis for longitudinal studies to build a solid foundation for reproducible analysis
Authors: Lusa Lara , Proust-Lima Ćecile , Schmidt Carsten O. , Lee Katherine J. , le Cessie Saskia , Baillie Mark , Lawrence Frank , Huebner Marianne
Published: December 2023

Initial data analysis (IDA) is the part of the data pipeline that takes place between the end of data retrieval and the beginning of data analysis that addresses the research question. Systematic IDA and clear reporting of the IDA findings is an important step towards reproducible research. A general framework of IDA for observational studies includes data cleaning, data screening, and possible updates of pre-planned statistical analyses. Longitudinal studies, where participants are observed repeatedly over time, pose additional challenges, as they have special features that should be taken into account in the IDA steps before addressing the research question. We propose a systematic approach in longitudinal studies to examine data properties prior to conducting planned statistical analyses.

In this paper we focus on the data screening element of IDA, assuming that the research aims are accompanied by an analysis plan, meta-data are well documented, and data cleaning has already been performed. IDA screening domains are participation profiles over time, missing data, and univariate and multivariate descriptions, and longitudinal aspects. Executing the IDA plan will result in an IDA report to inform data analysts about data properties and possible implications for the analysis plan that are other elements of the IDA framework.

Our framework is illustrated focusing on hand grip strength outcome data from a data collection across several waves in a complex survey. We provide reproducible R code on a public repository, presenting a detailed data screening plan for the investigation of the average rate of age-associated decline of grip strength.

With our checklist and reproducible R code we provide data analysts a framework to work with longitudinal data in an informed way, enhancing the reproducibility and validity of their work.
LEFT ATRIAL APPENDAGE CLOSURE IN PATIENTS WITH MECHANICAL MITRAL VALVE PROSTHESIS: A MULTICENTER ITALIAN PILOT STUDY
Authors: Preda Alberto , Margonato Davide , Gaspardone Carlo , Rizza Vincenzo , Vella Ciro , Rampa Lorenzo , Marzi Alessandra , Guarracini Fabrizio , della Bella Paolo , Agricola Eustachio , Gaspardone Achille , Montorfano Matteo , Mazzone Patrizio
Published: December 2023

Background

In patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutical INR range the incidence of cardiac thromboembolism is not negligible and the subgroup carrying a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients carriers of mechanical PMV who experienced a failure of VKA therapy.

Methods

In this retrospective, multicenter study, patients who underwent LAAC because of thrombotic events including TIA/stroke, systemic embolism and evidence of left atrial appendage thrombosis/sludge during VKA therapy were enrolled. Patients with mechanical PMV were included and compared with controls. The primary endpoint was the composite of all-cause death, major cardiovascular events and major bleedings at follow-up. Feasibility and safety of LAAC was also assessed.

Results

A total of 55 patients (42% females; mean age 70 ± 9 years) including 12 carriers of mechanical PMV were enrolled. The most frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases and in 100% of patients with PMV. In 35 patients a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with PMV and 20 patients without PMV reported adverse events (HR 0.73 [95% CI 0.25 – 2.16, p=0.564]).

Conclusion

LAAC seems to be a valuable alternative in AF patients with failure of VKA therapy who are carriers of mechanical PMV. This off-label, real-world clinical practice indication deserve validation in further studies.
Association between frequency of rehabilitation therapy and long-term mortality after stroke : a nationwide cohort study
Authors: Nam Je Shik , Heo Seok-Jae , Kim Yong Wook , Lee Sang Chul , Yang Seung Nam , Yoon Seo Yeon
Published: December 2023

Background

Poststroke rehabilitation reportedly improves functional outcomes and minimizes disability. However, previous studies have demonstrated conflicting results regarding the effects of rehabilitation therapy on post-stroke mortality. Therefore, we aimed to investigate the association between rehabilitation therapy within the first six months after stroke and long-term all-cause mortality in patients with stroke using data from the Korean National Health Insurance System.

Methods

A total of 10,974 patients newly diagnosed with stroke using ICD-10 codes (I60-I64) between 2013 and 2019 were enrolled and followed-up for all-cause mortality until 2019. Post-stroke patients were categorized into three groups according to the frequency of rehabilitation therapy: no rehabilitation therapy, ≤ 40 sessions, and > 40 sessions. Cox proportional hazard models were used to assess the mortality risk according to rehabilitation therapy stratified by disability severity.

Results

Higher frequency of rehabilitation therapy was associated with significantly lower post-stroke mortality in comparison to no rehabilitation therapy (HR=0.88, 95% CI 0.79-0.9 9), especially among individuals with severe disability after stroke (HR=0.74, 95% CI 0.62-0.87). An inverse association between number of rehabilitation therapy sessions and mortality was identified in a multivariate Cox regression model with restricted cubic splines. In the context of stroke type, higher frequency of rehabilitation therapy was associated with reduced mortality rates compared to no rehabilitation therapy only in patients with hemorrhagic stroke (HR=0.60, 95% CI 0.49-0.74). While socioeconomic factors were not associated with mortality, older age, male sex, and pneumonia were associated with increased mortality risk, regardless of disability severity.

Conclusions

Post-stroke rehabilitation therapy within six months of stroke onset seems to play a substantial role in reducing long-term mortality after stroke. A higher frequency of rehabilitation therapy is recommended for post-stroke patients, particularly among those with severe disability.
Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis
Authors: Mukherjee Monica , Strom Jordan B. , Afilalo Jonathan , Hu Mo , Beussink-Nelson Lauren , Kim Jiwon , Addetia Karima , Bertoni Alain , Gottdiener John , Michos Erin D. , Gardin Julius M. , Shah Sanjiv J. , Freed Benjamin H.
Published: December 2023

Background

Echocardiographic (2DE) thresholds indicating disease or impaired functional status compared to normal physiologic aging in individuals ≥ 65 years are not clearly defined. In the present study, we sought to establish standard values for 2DE parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions.

Methods

In this cross-sectional study of 3032 individuals who underwent 2DE at Exam 6 in the Multi-Ethnic Study of Atherosclerosis (MESA), 608 participants fulfilled our inclusion criteria, with normative values defined as the mean value ± 1.96 standard deviations and compared across sex and race/ethnicity. Functional status measures included NT-proBNP, 6-minute walk distance [6MWD], and Kansas City Cardiomyopathy Questionnaire [KCCQ]. Prognostic performance using MESA cutoffs was compared to established guideline cutoffs using time-to-event analysis.

Results

Participants meeting our inclusion criteria (69.5 ± 7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6MWD, and higher (better) KCCQ summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, while Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities.

Conclusions

Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function across sexes and races/ethnicities, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.
Detecting and understanding meaningful cancerous mutations based on computational models of mRNA splicing
Authors: Lynn Nicolas , Tuller Tamir
Published: December 2023

Cancer research has long relied on non-silent mutations. Yet, it has become overwhelmingly clear that silent mutations can affect gene expression and cancer cell fitness. One fundamental mechanism that apparently silent mutations can severely disrupt is alternative splicing. Here we introduceOncosplice, a tool that scores mutations based on models of proteomes generated using aberrant splicing predictions.Oncospliceleverages a highly accurate neural network that predicts splice sites within arbitrary mRNA sequences, a greedy transcript constructor that considers alternate arrangements of splicing blueprints, and an algorithm that grades the functional divergence between proteins based on evolutionary conservation. By applying this tool to 12M somatic mutations we identify 8K deleterious variants that are significantly depleted within the healthy population; we demonstrate the tool’s ability to identify clinically validated pathogenic variants with a positive predictive value of 94%; we show strong enrichment of predicted deleterious mutations across pan-cancer drivers. We also achieve improved patient survival estimation using a proposed set of novel cancer-involved genes. Ultimately, this pipeline enables accelerated insight-gathering of sequence-specific consequences for a class of understudied mutations and provides an efficient way of filtering through massive variant datasets – functionalities with immediate experimental and clinical applications.
Unravelling effects of fine-scale changes within wild-bird flocks on sociality
Authors: Troisi C.A. , Firth J.A. , Crofts S.J. , Davidson G.L. , Reichert M.S. , Quinn J.L.
Published: December 2023

Social structure and individual sociality impact a wide variety of behavioural and ecological processes. Although it is well known that changes in the physical and social environment shape sociality, how perturbations govern sociality at a fine spatial scale remains poorly understood. By applying automated experimental treatments to RFID-tracked wild great tits (Parus major) in a field experiment, we examined how individual social network metrics changed when food resources and social stability were experimentally manipulated at the within-group spatial scale.

First, we examined how individual sociality responds when food resources changed from a dispersed distribution (50m apart) to a clustered distribution (1m apart). Second, we tested how sociality changed when individuals were restricted to feeding in a manner that mimics assortative behaviour within flocks. Third, we tested the effects of experimentally manipulating the stability of these social groupings. Finally, we returned the feeders to the original dispersed distribution to test whether effects carried over.

Repeatability analyses showed consistent differences among individuals in their social phenotypes across the various manipulations; dyadic association preferences also showed consistency. Nevertheless, average flock size and social centrality measures increased after the food was clustered. Some of these metrics changed further when birds were then forced to feed from only one of the five clustered feeders. There was some support for group stability at individual feeders also impacting individual social network metrics: increase in flock size was more pronounced in the stable than the unstable group. Most of the differences in sociality were maintained when the food distribution returned to the dispersed pattern, and this was caused primarily by the change in resource distribution rather than the social manipulation.

Our results show that perturbations in the access to resources and social group stability can change sociality at a surprisingly fine spatial scale. These small-scale changes could arise through a variety of mechanisms, including assortative positioning within groups due to, for instance, similarity among individuals in their preferences for different resource patches. Our results suggest that small-scale effects could lead to social processes at larger scales and yet are typically overlooked in social groups.
Leaf- and diverged shoot meristem programs shape the stem in rice
Authors: Tsuda Katsutoshi , Maeno Akiteru , Otake Ayako , Kato Kae , Tanaka Wakana , Hibara Ken-Ichiro , Nonomura Ken-Ichi
Published: December 2023

The stem is the shoot axis in seed plants and has been a primary target in breeding to regulate crop height. However, early processes of stem development remain elusive. Here we show that regulators for shoot meristems and leaves determine the node-internode pattern in rice. Mutants ofKNOX1genesOSH15andOSH1, known to maintain shoot meristem indeterminacy1,2, showed dwarfism due to enlarged nodes and diminished internodes. These genes confine node differentiation by repressing leaf developmental regulatorYABBYgenes in internodal vasculatures.YABBYexpression, which normally extends from leaves to nodes along vasculatures, promotes nodal vascular differentiation and limits stem elongation. It expands inknox1mutants, and the loss ofYABBYgenes reverts their dwarfism.OSH15also represses node-specificKNOX1subclade genesOSH6andOSH71to allow internode elongation. Importantly, bothYABBYand node-specificKNOX1genes are required for pulvinus formation at the leaf base, further elaborating the nodal structure for gravitropism. Thus, intersections between leaf and sub-functionalized shoot meristem programs shape nodes and internodes along the stem. Phylogenetic analysis showed thatKNOX1sub-functionalization likely occurred in the progenitor of gymnosperms and angiosperms. Given that seed plants acquired their leaves independently from other vascular plant lineages3,4, the emergence of the node-internode pattern andKNOX1-YABBYregulatory module may be linked to seed plant leaf evolution.
CHARACTERIZATION OF EARLY-MATURING COWPEA (Vigna unguiculata(L.) WALP.) GERMPLASMS THROUGH ASSOCIATION ANALYSIS
Authors: Ogbeche Iduh Michael , Ekeruo Godspower Chibuike , Vange T , Omoigui Lucky , Ogbu Odang Emmanuel , Oyinkansola Koletowo Faruq , Olalekan Ayeni
Published: December 2023

Early maturing cowpea is a valuable crop for sub-Saharan Africa that offers a number of benefits, including a short growing season, drought tolerance, and the potential to improve food security. This study was conducted to analyze character associations in genetically diverse cowpea (Vigna unguiculata(L.) Walp.) germplasm, employing ten distinct accessions within a randomized complete block design with four replicates. Parameters such as days to first flowering, days to fifty percent flowering, number of branches per plant, days to ninety-five percent maturity, number of pods per plant, hundred-seed weight, total pod weight, and total seed weight were subjected to analysis of variance (ANOVA), Correlation, and Path Coefficient Analysis. Results revealed significant positive correlations between “branches per plant and pods per plant (r = 0.317, p ≤ 0,001),” “pods per plant and pod weight (r = 0.136, p < ≤ 0,001),” and “pod weight and seed weight (r =0.567, p ≤ 0,001).” Path coefficient analysis identified pod weight (0.840938) as the most influential direct contributor to yield, while the number of pods (-0.04268) indirectly influenced yield through pod weight. High grain yield selection can be achieved through indirect manipulation of pod weight. Accession IT99K-573-1-1, IT10K-863-11 and IT08K-125-24 exhibited the highest yield characters (pod weight and seed weight) and therefore further studies is recommended to consolidate this work, to enhance adoption by farmers.